Laboratory of Organic Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
Angew Chem Int Ed Engl. 2018 May 4;57(19):5288-5291. doi: 10.1002/anie.201712554. Epub 2018 Apr 3.
Enzymes are valuable biocatalysts for asymmetric synthesis due to their exacting stereocontrol. Changing the selectivity of an existing catalyst for new applications is, however, challenging. Here we show that, in contrast, the stereoselectivity of an artificial enzyme created by design and directed evolution is readily tunable. We engineered a promiscuous artificial retro-aldolase into four stereocomplementary catalysts for the Michael addition of a tertiary carbanion to an unsaturated ketone. Notably, this selectivity is also preserved with alternative Michael nucleophiles. Complete stereodiversification of other designer enzymes should similarly be possible by extension of these approaches.
酶是不对称合成中非常有价值的生物催化剂，因为它们具有精确的立体控制。然而，改变现有催化剂的选择性以适应新的应用是具有挑战性的。在这里，我们表明，与现有催化剂不同，通过设计和定向进化创造的人工酶的立体选择性是易于调节的。我们将一种混杂的人工 retro-aldolase 工程化为四种立体互补的催化剂，用于叔碳负离子与不饱和酮的迈克尔加成。值得注意的是，这种选择性也可以通过其他迈克尔亲核试剂保留。通过扩展这些方法，其他设计酶的完全立体多样化也应该是可能的。
